PEA ‑15 contributes to the clinicopathology and AKT‑regulated cisplatin resistance in gastric cancer.

PEA‑15 contributes to the clinicopathology and AKT‑regulated cisplatin resistance in gastric cancer. Oncol Rep. 2018 Dec 18;: Authors: Jiang X, Zhang C, Li W, Jiang D, Wei Z, Lv M, Xie X, Sun X Abstract Phosphoprotein enriched in astrocytes 15 (PEA‑15) plays an important role in controlling biological behaviors of cancer cells. In the present study, we demonstrated that PEA‑15 was overexpressed in gastric cancer tissues and associated with tumor staging, differentiation, pathological types and the prognosis of patients. Gastric cancer cells expressed variable levels of PEA‑15 and its bi‑phosphorylation forms, p‑PEA‑15 (Ser104) and p‑PEA‑15 (Ser116). To gain insight into the functional role of PEA‑15, we generated cells stably depleted of PEA‑15 and resistant to cisplatin (CDDP) from human gastric cancer cells. PEA‑15 depletion inhibited cell proliferation by reducing cyclin D1 expression through the extracellular signal‑regulated kinase (ERK) pathway, resulting in cell cycle arrest at the G1 phase, and induced apoptosis by activating caspase‑8. PEA‑15 depletion also enhanced the inhibitory effect of CDDP that caused cell cycle arrest at the S phase and also enhanced the pro‑apoptotic activity of CDDP in vitro and in animal models of tumorigenesis and therapeutic effects. PEA‑15 and its phosphorylated forms were overexpressed in CDDP‑resistant cells, which had higher levels of p‑AKT. Specific in...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research